PROJECT SUMMARY/ABSTRACT This is a new application for multidisciplinary predoctoral training in discovery and translational research at Mayo Clinic in the inter-related fields of Diabetes and Metabolic Disease, Digestive Diseases and Gastroenter- ology, and Kidney Disease and Hypertension (DDK). The overarching objective is to develop a diverse pool of well-trained biomedical career scientists with the experience and skillsets to become leaders in the next gener- ation of DDK researchers. Two senior and accomplished Mayo scientists with an extensive background in graduate education and mentoring will co-direct this program centered upon four Mechanism-Centric Research Communities in i) Bioengineering and Biophysical Analysis, ii) Cell-to-Cell Communication, iii) Genomic Regu- lation, and iv) Intracellular Signaling, with 24 interdisciplinary faculty members and over $20 million in funding. This core DDK faculty provides a robust infrastructure with a successful history of training career scientists in discovery-based and translational biomedical research. These laboratories offer a rich mentoring and training environment that is uniquely tailored to the individual student while also promoting collective experiences across multiple disciplines. The program's Specific Aims focus on fundamental aspects of reproducible and rigorous biomedical research that align with NIH/NIDDK priorities. These are to: i) Offer a solid foundation in scientific reasoning, research design, rigor, quantitative experimental approaches and analysis of datasets, with objective interpretation of results; ii) Foster broad multidisciplinary understanding combined with critical independent thinking skills, while implementing the ability to identify outstanding biomedical questions and ini- tiate new approaches to advance the field; iii) Develop effective oral and written communication skills across diverse audiences; iv) Promote ethical conduct in biomedical research and team skills that facilitate collabora- tive scientific research alongside colleagues while promoting an inclusive work environment; v) Provide the background to identify and effectively transition into productive basic and clinical DDK investigators. The pro- gram strongly supports synergistic interactions between Mayo Clinic Basic Science Departments and NIDDK- funded Centers in Digestive Disease, Translational PKD, and Pathobiology of the Enteric System. The stu- dents will actively engage in a full array of programmatic activities, including journal clubs, seminar and works- in-progress series, career and professional development events, annual retreat, Mayo Graduate School wide symposium and poster session, along with participation in national meetings and others. These activities syn- ergize with three related DDK postdoctoral programs at Mayo Clinic in Diabetes and Metabolism, Digestive Diseases, and Kidney Disease, while offering a complete continuum from summer undergraduate research experiences through PhD and postdoctoral training. Requirements for completion of the PhD degree conform to Mayo Graduate School requirements, including a first author publication. The program draws from a strong pool of 75+ qualified Mayo Clinic graduate students; we request support for six predoctoral trainees per year.